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25 March 2006

Extreme Gene Expression: Taking Proteomics to the Next Level

Researchers are moving beyond mere genomics into proteomics--where most of the work of the cell is actually done. This newsrelease from the University of Toronto reports on the newest discoveries in protein-protein interactions.

The findings, which will be released in the March 30 issue of Nature, reveal how researchers used sophisticated proteomic techniques to identify close to 4,000 proteins and 550 protein complexes involved in 7,123 protein-protein interactions in yeast cells, about half of which are novel. Many of the same complexes and protein interactions that go awry in human disease are also found in yeast. While living yeast cells have only 6,000 genes compared to a human’s 25,000, the structures of their encoded proteins and interactions among the proteins are virtually identical to ours.

“Human proteins involved in disease and protein interactions gone awry found in humans are often found in yeast,” says Professor Andrew Emili of U of T’s Banting and Best Department of Medical Research, the study’s co-author. “By studying and mapping out sets of protein interactions within this basic organism, we are providing the foundation to move into a more complex organism such as a mouse and then a human.”

To map the protein complexes within the cell, researchers combined purification techniques with analysis using mass spectrometry, a technique that breaks down and identifies chemical substances within molecules. Using the combined approach of purification and mass spectrometry, the researchers were able to ensure accuracy and reveal more than 250 complexes that have not yet been reported in previous public databases. The researchers have posted their current findings on a publicly available comprehensive database (http://tap.med.utoronto.ca) and hope the findings will spur further advances within the scientific community. “This database will be linked with other sites, so that results can be compared and contrasted,” says co-author Professor Jack Greenblatt, also of U of T’s Banting and Best Department of Medical Research. “The methods we used to identify protein interactions and protein complexes in yeast appear to be the best currently available, and so are likely to be used soon to identify protein interactions involved in human disease.”

....The next step, according to Emili, is to analyse these new complexes to determine their roles in living cell functions. “Now that we have the pieces of the puzzle, we have to put them together to get the overall picture,” Emili says. “It is painstaking work, but it brings us closer to answer science’s most fundamental question: how does life operate?”